When you hold an object, a sudden unexpected perturbation can threaten the stability of your grasp. In such situations grasp stability is maintained by fast reflexive-like grip force responses triggered by the somatosensory feedback. Here we use functional magnetic resonance imaging (fMRI) to investigate the neural mechanisms involved in the grip force responses associated with unexpected increases (loading) and decreases (unloading) in the load force. Healthy right-handed subjects held an instrumented object (of mass 200 g) between the tips of right index finger and thumb. At some time during an interval of 8 to 45 seconds the weight of the object was suddenly increased or decreased by 90 g. We analyzed the transient increases in the fMRI signal that corresponded precisely in time to these grip force responses. Activity in the left primary motor cortex was associated with the loading response, but not with unloading, suggesting that sensorimotor processing in this area mediates the sensory triggered reflexive increase in grip force during loading. Both the loading and the unloading events activated the cingulate motor area and the medial cerebellum. We suggest that these regions could participate in the updating of the sensorimotor representations of the fingertip forces. Finally, the supplementary somatosensory area located on the medial wall of the parietal lobe showed an increase in activity only during unloading, indicating that this area is involved in the sensorimotor processing generating the unloading response. Taken together, our findings suggest different central mechanisms for the grip force responses during loading and unloading.